{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T05:44:11Z","timestamp":1791870251337,"version":"4.3.4"},"reference-count":40,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Medical Research Centre of Radiology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ischemic stroke remains a leading cause of death and disability worldwide, with neuroinflammation playing a central role in its pathogenesis. This study aimed to investigate age-related differences in neuroinflammatory responses in the human cerebral cortex following ischemic stroke. Using autopsy-derived brain tissue from 184 patients histological, histochemical, multiplex immunofluorescence, ELISA, and qRT-PCR analyses were conducted to assess neuronal damage, immune cell infiltration and cytokine expression. Morphological examination revealed pannecrosis in infarct cores and moderate inflammatory infiltration in penumbral regions. Multiplex immunofluorescence demonstrated active migration of NK (CD45+CD56+CD3\u2212) and NKT (CD45+CD56+CD3+) cells in young patients, whereas elderly individuals showed a predominance of T lymphocytes (CD45+CD56\u2212CD3+) and a decline in NK\/NKT activity. Molecular assays indicated elevated NKG2D receptor expression and higher IFN-\u03b3 and proinflammatory cytokine (TNF-\u03b1, IL-1\u03b2, IL-6) levels in young patients, contrasting with dysregulated cytokine balance and reduced NK cytotoxicity in the elderly. These findings highlight distinct age-dependent immune mechanisms underlying ischemic injury, demonstrating that NK and NKT cells play a crucial role in early neuroinflammation, while aging shifts the balance toward adaptive immune dominance. The study underscores the need to consider patient age when designing neuroprotective and anti-inflammatory therapeutic strategies for ischemic stroke.<\/jats:p>","DOI":"10.3390\/ijms262311452","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T14:39:43Z","timestamp":1764167983000},"page":"11452","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Age-Related Features of Neuroinflammation: Hidden Association of Neuronal Damage with Activation of Natural Killers in Patients with Ischemic Stroke"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6235-1020","authenticated-orcid":false,"given":"Matvey","family":"Vadyukhin","sequence":"first","affiliation":[{"name":"Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky Pass., 3, 125284 Moscow, Russia"},{"name":"Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya st., 8\/2, 119048 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6946-6146","authenticated-orcid":false,"given":"Tatiana","family":"Demura","sequence":"additional","affiliation":[{"name":"Institute of Clinical Morphology and Digital Pathology, I.M. Sechenov First Moscow State Medical Univesity (Sechenov University), Trubetskaya st., 8\/2, 119048 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1107-3753","authenticated-orcid":false,"given":"Eugenia","family":"Kogan","sequence":"additional","affiliation":[{"name":"Institute of Clinical Morphology and Digital Pathology, I.M. Sechenov First Moscow State Medical Univesity (Sechenov University), Trubetskaya st., 8\/2, 119048 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3763-7454","authenticated-orcid":false,"given":"Vladimir","family":"Shchekin","sequence":"additional","affiliation":[{"name":"Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky Pass., 3, 125284 Moscow, Russia"},{"name":"Research and Educational Resource Center for Immunophenotyping, Digital Spatial Profiling and Ultrastructural Analysis Innovative Technologies, Peoples\u2019 Friendship University of Russia (RUDN University), Miklukho-Maklaya st., 6, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9755-1164","authenticated-orcid":false,"given":"Petr","family":"Shegai","sequence":"additional","affiliation":[{"name":"Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky Pass., 3, 125284 Moscow, Russia"},{"name":"Department of Urology and Operative Nephrology, Peoples\u2019 Friendship University of Russia (RUDN University), Miklukho-Maklaya st., 6, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8784-8415","authenticated-orcid":false,"given":"Andrey","family":"Kaprin","sequence":"additional","affiliation":[{"name":"Department of Digital Oncomorphology, National Medical Research Centre of Radiology, 2nd Botkinsky Pass., 3, 125284 Moscow, Russia"},{"name":"Department of Urology and Operative Nephrology, Peoples\u2019 Friendship University of Russia (RUDN University), Miklukho-Maklaya st., 6, 117198 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8447-2600","authenticated-orcid":false,"given":"Grigory","family":"Demyashkin","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine and Biotechnology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya st., 8\/2, 119048 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e16481","DOI":"10.1111\/ene.16481","article-title":"Global, regional, and national epidemiology of ischemic stroke from 1990 to 2021","volume":"31","author":"Hou","year":"2024","journal-title":"Eur. J. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Xu, J., Hou, S., Chen, Z., Liu, Y., Deng, X., Wang, C., Liu, S., and Wang, Y. (2025). The burden of ischemic stroke in Eastern Europe from 1990 to 2021. 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